This study represents one portion of a major program in our laboratory whose objectives are to 1) understand the mechanisms of action involved in the selective radio- and chemo-sensitization of neoplastic tissues and cells by hyperthermia, and 2) utilize this knowledge in the treatment of cancer. To this end animal studies, in vitro cellular studies and clinical studies are currently under way. The objective of the present proposal is to compare the response of neoplastic and normal tissues of the mouse to local tumor hyperthermia (LTH) and radiation to evaluate the time-dose relationship of combined radiation and hyperthermia on the therapeutic ratio. It is proposed that these studies be carried out using the Meth A tumor grown in the right thigh of BALB/c male mice. The legs will be exposed to several doses of radiation alone or in combination with heat to establish the TCD50 for varying numbers of fractionated treatments. The TCD50 curves will be plotted vs. time and compared to the skin, muscle and nerve/muslce resonse of the treated area. Comparisons of the time-dose response of the tumor vs. normal tissues will help establish fractionation schemes which will optimize the therapeutic ratio.